This proposal is an R 21 NIH Exploratory/Developmental Grant in response to PA-09-164. It focuses on the potential predictive value of assessment of specific cognitive processing skills (namely, executive function skills and memory function skills, as indexed by both neurocognitive tests and functional and structural neuroimaging) to outcomes in cognitive-behavioral therapy (CBT) for late-life depression (LLD). The title of the proposal is: "Predictors of Positive Outcome in Cognitive Behavior Therapy for Late Life Depression." Despite advances in both pharmacotherapy and psychotherapy for the treatment of LLD, relatively little research has been conducted on biological and neuropsychological predictors of treatment success. Since CBT is a form of therapy that requires considerable cognitive processing over a period of time, and since about one-third of older patients treated with CBT have not achieved remission of their depressed status by the end of therapy, there is a need to identify specific predictors that could be useful in making decisions about the appropriateness of one form of treatment over another. For example, if patients with compromised cognitive skills do poorly in CBT, then that would suggest both evaluation before assignment to treatment (to determine level of cognitive functioning) and, most likely, assignment to a different form of treatment: not CBT. Although in this study we will not be comparing treatments for LLD, but instead using only the one modality of CBT, we believe this is justified at this point, since CBT is the most widely used form of psychotherapy for LLD, and only a few studies have been conducted to evaluate neural substrates associated with success, and/ or cognitive processing skills in CBT - but these have not been conducted specifically with older adults. Given that decrements in many cognitive skills seem to be associated with aging, along with changes in the structure and function of the brain, it would seem timely to study these complex inter- relationships, and their relationship to CBT outcome, in the proposed pilot study. Prior studies that found that both executive functioning skills and memory functioning skills may be associated with responsiveness to psychotherapy -though typically they did not include patients over 60 years of age in the sample. Other research has found that hypoactivation of the prefrontal cortex, and hyperactivation of the amygdala, are often associated with maintenance of depression and some would say, treatment resistance. Again, these studies do not focus on older patients, who may have neurocognitive changes, along with structural and functional brain changes, due to aging and/or other underlying pathophysiology (e.g., Alzheimer's disease or another form of dementia). Given this paucity of information on how these variables might, independently and in combination, be associated with responsiveness to CBT, this pilot study seems warranted, and its findings will be informative for future research and clinical care. In the proposed study, 75 depressed out- patients age 60 and above will be recruited to receive 16 to 20 sessions of CBT over a 4 -5 month period. A neurocognitive battery designed to measure executive function, memory, attentional processing and language processing will be administered prior to therapy. A functional MRI and a resting MRI will also be obtained. Specific measures in these three domains will serve as independent variables in statistical analyses to identify specific combinations of factors that will predict response to therapy with maximal efficiency. PUBLIC HEALTH RELEVANCE: This proposal is an R 21 NIH Exploratory/Developmental Grant in response to PA-09-164. It focuses on the potential predictive value of assessment of specific cognitive processing skills (namely, executive function skills and memory function skills, as indexed by both neurocognitive tests and functional and structural neuroimaging) to outcomes in cognitive-behavioral therapy (CBT) for late-life depression (LLD). The title of the proposal is: "Predictors of Positive Outcome in Cognitive Behavior Therapy for Late Life Depression." Despite advances in both pharmacotherapy and psychotherapy for the treatment of LLD, relatively little research has been conducted on biological and neuropsychological predictors of treatment success. This project focuses on novel predictors obtained from neurocognitive and neurocognitive indices combined. It has important public health implications because it will assist in identification of appropriate treatments for specific individuals based on their cognitive processing profiles.